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Brain Gαi2-subunit protein-gated pathways are required to mediate the centrally evoked sympathoinhibitory mechanisms activated to maintain sodium homeostasis.
J Hypertens 2013; 31(4):747-57JH

Abstract

OBJECTIVE

We have previously demonstrated a role of GPCR-activated brain Gαi(2)-subunit protein-gated pathways in the natriuretic responses evoked by exogenous central α(2)-adrenoceptor activation and acute intravenous (i.v.) volume expansion in vivo. Our objective was to examine the role of brain Gαi(2) proteins in the integrated neural-humoral responses evoked by i.v. isovolumetric sodium loading, which does not alter mean arterial blood pressure or total blood volume, to maintain sodium homeostasis in conscious Sprague-Dawley rats.

METHODS

Intact or chronic bilateral renal denervated (RDNX) rats were pretreated intracerebroventricularly (i.c.v.) with a scrambled or Gαi(2) oligodeoxynucleotide to selectively downregulate brain Gαi(2) proteins. On the day of study, an i.v. isovolumetric sodium load (1 mol/l NaCl) was administered.

RESULTS

In naive and scrambled oligodeoxynucleotide groups, i.v. sodium loading evoked profound natriuresis, suppression of plasma renin activity (PRA) and global sympathoinhibition. Prior downregulation of brain Gαi(2) proteins significantly attenuated the natriuretic response [peak ΔUNaV (μeq/μl); scrambled 22 ± 2 vs. Gαi(2) 13 ± 2, P < 0.05] and abolished the sympathoinhibitory response [peak Δplasma norepinephrine (% control); SCR -72 ± 8 vs. Gαi(2) -7 ± 5, P < 0.05] without attenuating PRA suppression to sodium loading. In RDNX rats, Gαi(2) oligodeoxynucleotide pretreatment failed to attenuate the natriuretic response [peak ΔUNaV (μeq/μl); RDNX and scrambled 19 ± 3 vs. RDNX and Gαi(2) 20 ± 2] and only partially prevented the sympathoinhibitory response to i.v. sodium loading.

CONCLUSION

These studies reveal a brain Gαi(2)-subunit protein-mediated (renin-angiotensin system-independent) sympathoinhibitory pathway that has a critical role in the central neural mechanisms activated to maintain fluid and electrolyte homeostasis.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics and the Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. rwainf@bu.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23391983

Citation

Wainford, Richard D., et al. "Brain Gαi2-subunit Protein-gated Pathways Are Required to Mediate the Centrally Evoked Sympathoinhibitory Mechanisms Activated to Maintain Sodium Homeostasis." Journal of Hypertension, vol. 31, no. 4, 2013, pp. 747-57.
Wainford RD, Pascale CL, Kuwabara JT. Brain Gαi2-subunit protein-gated pathways are required to mediate the centrally evoked sympathoinhibitory mechanisms activated to maintain sodium homeostasis. J Hypertens. 2013;31(4):747-57.
Wainford, R. D., Pascale, C. L., & Kuwabara, J. T. (2013). Brain Gαi2-subunit protein-gated pathways are required to mediate the centrally evoked sympathoinhibitory mechanisms activated to maintain sodium homeostasis. Journal of Hypertension, 31(4), pp. 747-57. doi:10.1097/HJH.0b013e32835ebd54.
Wainford RD, Pascale CL, Kuwabara JT. Brain Gαi2-subunit Protein-gated Pathways Are Required to Mediate the Centrally Evoked Sympathoinhibitory Mechanisms Activated to Maintain Sodium Homeostasis. J Hypertens. 2013;31(4):747-57. PubMed PMID: 23391983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain Gαi2-subunit protein-gated pathways are required to mediate the centrally evoked sympathoinhibitory mechanisms activated to maintain sodium homeostasis. AU - Wainford,Richard D, AU - Pascale,Crissey L, AU - Kuwabara,Jill T, PY - 2013/2/9/entrez PY - 2013/2/9/pubmed PY - 2013/8/30/medline SP - 747 EP - 57 JF - Journal of hypertension JO - J. Hypertens. VL - 31 IS - 4 N2 - OBJECTIVE: We have previously demonstrated a role of GPCR-activated brain Gαi(2)-subunit protein-gated pathways in the natriuretic responses evoked by exogenous central α(2)-adrenoceptor activation and acute intravenous (i.v.) volume expansion in vivo. Our objective was to examine the role of brain Gαi(2) proteins in the integrated neural-humoral responses evoked by i.v. isovolumetric sodium loading, which does not alter mean arterial blood pressure or total blood volume, to maintain sodium homeostasis in conscious Sprague-Dawley rats. METHODS: Intact or chronic bilateral renal denervated (RDNX) rats were pretreated intracerebroventricularly (i.c.v.) with a scrambled or Gαi(2) oligodeoxynucleotide to selectively downregulate brain Gαi(2) proteins. On the day of study, an i.v. isovolumetric sodium load (1 mol/l NaCl) was administered. RESULTS: In naive and scrambled oligodeoxynucleotide groups, i.v. sodium loading evoked profound natriuresis, suppression of plasma renin activity (PRA) and global sympathoinhibition. Prior downregulation of brain Gαi(2) proteins significantly attenuated the natriuretic response [peak ΔUNaV (μeq/μl); scrambled 22 ± 2 vs. Gαi(2) 13 ± 2, P < 0.05] and abolished the sympathoinhibitory response [peak Δplasma norepinephrine (% control); SCR -72 ± 8 vs. Gαi(2) -7 ± 5, P < 0.05] without attenuating PRA suppression to sodium loading. In RDNX rats, Gαi(2) oligodeoxynucleotide pretreatment failed to attenuate the natriuretic response [peak ΔUNaV (μeq/μl); RDNX and scrambled 19 ± 3 vs. RDNX and Gαi(2) 20 ± 2] and only partially prevented the sympathoinhibitory response to i.v. sodium loading. CONCLUSION: These studies reveal a brain Gαi(2)-subunit protein-mediated (renin-angiotensin system-independent) sympathoinhibitory pathway that has a critical role in the central neural mechanisms activated to maintain fluid and electrolyte homeostasis. SN - 1473-5598 UR - https://www.unboundmedicine.com/medline/citation/23391983/Brain_Gαi2_subunit_protein_gated_pathways_are_required_to_mediate_the_centrally_evoked_sympathoinhibitory_mechanisms_activated_to_maintain_sodium_homeostasis_ L2 - http://dx.doi.org/10.1097/HJH.0b013e32835ebd54 DB - PRIME DP - Unbound Medicine ER -